title: Acute tubular necrosis associated with mTOR inhibitor therapy: a real entity biopsy-proven.
abstract: BACKGROUND
  The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. Inhibitors of mTOR have immunosuppressive and anti-cancer effects, but their effects on the progression of kidney disease are not fully understood. Their most common side-effects include stomatitis, rash, dyslipidemia, hyperglycemia, fatigue, and pneumonitis. However, to the best of our knowledge these agents have not been previously reported to cause severe acute kidney injury (AKI).
  
  
  METHODS
  We describe four cases of patients with cancer who developed AKI after starting mTOR inhibitor therapy. A kidney biopsy showed acute tubular necrosis (ATN) with prominent tubular dysfunction. Withdrawal of the drug leads to a rapid recovery in two cases. However, a fixed renal dysfunction was noted in the other two cases, one of which will remain dialysis-dependent. Such patients lead to a broad differential diagnosis of AKI including prerenal AKI, ATN, cancer-related GN, and drug-induced acute interstitial nephritis. Accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients.
  
  
  CONCLUSIONS
  ATN have not been reported with mTOR inhibitor use. These cases demonstrated a potentially new and serious adverse consequence occurring with the use of an mTOR inhibitor, of which physicians need to be aware.
authors.affiliation: Department of Nephrology, Pitié-Salpêtrière Hospital, Paris, France. hassan.izzedine@psl.aphp.fr
authors.forename: H
authors.initials: H
authors.lastname: Izzedine
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.forename: P
authors.initials: P
authors.lastname: Rouvier
authors.forename: V
authors.initials: V
authors.lastname: Gueutin
authors.forename: A
authors.initials: A
authors.lastname: Varga
authors.forename: R
authors.initials: R
authors.lastname: Bahleda
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000601:surgery; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy; D008875:Middle Aged; D009336:Necrosis; D009392:Nephrectomy; D000068437:Pemetrexed; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005971:Glutamates; D007093:Imidazoles; D007211:Indoles; D011758:Pyrroles; D000068437:Pemetrexed; D014750:Vincristine; D006147:Guanine; D000077211:Zoledronic Acid; D004317:Doxorubicin; D003520:Cyclophosphamide; D007372:Interferons; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin; D000077210:Sunitinib; D011241:Prednisone
keywords: acute renal failure; acute tubular necrosis; mTOR